Project Summary The long-term goal of this study is to develop a biomarker-based screening assay for the early detection of AD-related biochemical changes that can be measured in biofluids such as the CSF. The main goal of this study is to identify phage-based probes to novel protein metabolites associated with AD and its progression. This study will have multiple positive effects that include: earlier and more accurate diagnosis and improved ability to monitor disease progression. To accomplish this goal the project has two aims: Aim. Identify phage with high sensitivity and specificity for AD-related post-translational modifications (PTMs) to selected proteins associated with AD. This aim will leverage the power of phage display to identify novel biomarkers within a selected group of proteins previously found to be associated with AD. Preliminary data demonstrate the proposed method is sufficient to differentially identify even closely related metabolites as well as differentiate between a pilot group of clinically diagnosed AD and control subjects. Alzheimer?s disease is a slow, progressive neurodegenerative disease that ultimately results in death. It is the 6th leading cause of death in the U.S. and there is no cure. Currently, diagnosis occurs relatively late in the, and many cases of AD are misdiagnosed. This proposal addresses an important gap in the development of robust biomarker arrays to assist in the more accurate and earlier detection of AD-related dementia. Completion of this study would be the first step to create PTM based array to evaluate the range of AD-relevant biomarkers to further improve the accuracy of diagnosis and monitoring of disease progression.